16 Clinical Utility of the Modified Prothrombin Time Test As Part of an Emergency Stroke Panel. (11th January 2018) - Eckel, Ashley
Abstract: Stroke is a leading cause of serious, long-term disability and the fifth leading cause of death in the United States. Thrombolytic therapy, specifically with intravenous (IV) recombinant tissue plasminogen activator (tPA) can restore cerebral blood flow in some patients with acute ischemic stroke and may lead to improvement or resolution of neurologic defects. The administration of tPA is highly time sensitive, as the medication must be given within 3.0–4.5 hours of symptom onset. In addition to the time limitations, there are several other contraindications to the administration of tPA, including thrombocytopenia and coagulopathies, particularly current use of an anticoagulant. In order to address the hematologic contraindications to tPA administration, our institution offers an Emergency Stroke Panel, a STAT test including platelet count, hematocrit, fibrinogen, prothrombin time (PT) and thrombin time (TT). Although the traditional PT and TT assays are adequate for monitoring the effects of conventional oral anticoagulants, such as warfarin and dabigatran, we find they are they are not suitable for accurate measurement of the direct oral anticoagulants (DOAC). These medications, which are becomingly increasingly more common, include the direct factor Xa inhibitors rivaroxaban, edoxaban, and apixaban. For this reason, we include in our panel a modified PT (mPT) assay. This test modifies the PT assay by adding calcium chloride (CaCl2 ) to the thromboplastin reagent to increase the dynamic range and improve sensitivity. In order to assess the utility of the mPT assay, we reviewed all orders of the Emergency Stroke panel at our two primary hospitals over the last two years, for a total of 395 patients tested with the panel. We also performed the PT, mPT, an activated partial thromboplastin time (aPTT), and an anti-Xa assay on multiple samples either from patients known to be taking DOAC or samples spiked with DOAC medications at clinically relevant concentrations. Our institution currently uses an INR of 1.7 as the cutoff for administration of tPA. For samples from patients known to be taking DOAC, as well as spiked samples, we found that 60% of rivaroxaban samples and 100% of apixaban samples yielded INR values less than 1.7. However, we found that 100% of the rivaroxaban samples and 80% of the apixaban samples could be detected using the mPT cutoffs we have established. In patients with suspected stroke, while warfarin use remained the most common reason for an elevated mPT value, the mPT was also able to detect rivaroxaban and apixaban use. Our study indicates that while factor Xa inhibitors generally do not require routine anticoagulant monitoring during clinical use, during specific emergent clinical circumstances such as stroke, the mPT can serve as a useful assay to monitor for their activity.